McDonnell Melissa J, Jary Hannah R, Perry Audrey, MacFarlane James G, Hester Katy L M, Small Therese, Molyneux Catherine, Perry John D, Walton Katherine E, De Soyza Anthony
Institute of Cellular Medicine Newcastle University and Adult Bronchiectasis Service, Department of Respiratory Medicine, The Freeman Hospital, Newcastle upon Tyne, UK.
Department of Medical Microbiology, The Freeman Hospital, High Heaton, Newcastle upon Tyne, NE7 7DN, England, UK.
Respir Med. 2015 Jun;109(6):716-26. doi: 10.1016/j.rmed.2014.07.021. Epub 2014 Aug 29.
The hallmark of non-cystic fibrosis bronchiectasis is recurrent bronchial infection, yet there are significant gaps in our understanding of pathogen persistence, resistance and exacerbation frequencies. Pseudomonas aeruginosa is a key pathogen thought to be a marker of disease severity and progression, yet little is known if the infection risk is seen in those with milder disease or if there is any potential for eradication. These data are important in determining risk stratification and follow up.
A retrospective review of consecutive adult patients attending a specialist UK bronchiectasis clinic over a two-year recruitment period between July 2007 and June 2009 was performed. Analysis of our primary outcome, longitudinal microbiological status, was recorded based on routine clinical follow-up through to data capture point or date of death. Patients were stratified by lung function and infecting organism.
155 patients (mean (SD) age 62.2 (12.4) years; 60.1% female) were identified from clinic records with microbiological data for a median (IQR) follow up duration of 46 (35-62) months. Baseline mean FEV1% predicted was 60.6% (24.8) with mean exacerbation frequency of 4.42/year; 73.6% reported 3 or more exacerbations/year. Haemophilus influenzae was isolated in 90 (58.1%) patients and P. aeruginosa in 78 (50.3%) patients with persistent infection in 51 (56.7%) H. influenzae and 47 (60.3%) P. aeruginosa, respectively. Of the P. aeruginosa colonised patients, 16 (34%) became culture negative on follow-up with a mean of 5.2 negative sputum cultures/patient. P. aeruginosa was isolated from 5 out of 39 patients (12.8%) with minimal airflow limitation as compared to 18 out of 38 patients (47.4%) with severe airflow limitation. Although hospital admissions were significantly higher in the P. aeruginosa infected group (1.3 vs. 0.7 admissions per annum, p = 0.035), overall exacerbation rates were the same (4.6 vs. 4.3, p = 0.58). Independent predictors of P. aeruginosa colonisation were low FEV1% predicted (OR 2.46; 95% CI 1.27-4.77) and polymicrobial colonisation (OR 4.07; 95% CI 1.56-10.58). 17 (11%) patients were infected with multi-resistant strains; however, none were pan-resistant.
P. aeruginosa is associated with greater persistent infection rates and more hospital admissions than H. influenzae. Exacerbation rates, however, were similar; therefore H. influenzae causes significant out-patient morbidity. P. aeruginosa infection occurs across all strata of lung function impairment but is infrequently multi-resistant in bronchiectasis. Careful microbiology follow up is required even in those with well-preserved lung function.
非囊性纤维化支气管扩张的标志是反复发生支气管感染,但我们对病原体持续存在、耐药性和急性加重频率的理解仍存在重大差距。铜绿假单胞菌是一种关键病原体,被认为是疾病严重程度和进展的标志,但对于病情较轻者是否存在感染风险或是否有根除的可能性知之甚少。这些数据对于确定风险分层和随访很重要。
对2007年7月至2009年6月为期两年的招募期内在英国一家专科支气管扩张诊所就诊的连续成年患者进行回顾性研究。基于常规临床随访直至数据采集点或死亡日期,记录我们的主要结局,即纵向微生物学状态。患者按肺功能和感染病原体进行分层。
从临床记录中确定了155例患者(平均(标准差)年龄62.2(12.4)岁;60.1%为女性),其微生物学数据的中位(四分位间距)随访时间为46(35 - 62)个月。预测的基线平均第一秒用力呼气容积(FEV1)百分比为60.6%(24.8),平均急性加重频率为4.42次/年;73.6%的患者报告每年有3次或更多次急性加重。90例(58.1%)患者分离出流感嗜血杆菌,78例(50.3%)患者分离出铜绿假单胞菌,其中分别有51例(56.7%)流感嗜血杆菌和47例(60.3%)铜绿假单胞菌持续感染。在铜绿假单胞菌定植的患者中,16例(34%)在随访时培养转为阴性,平均每位患者有5.2次痰培养阴性。在39例气流受限最小的患者中有5例(12.8%)分离出铜绿假单胞菌,而在38例严重气流受限的患者中有18例(47.4%)分离出该菌。虽然铜绿假单胞菌感染组的住院次数明显更高(每年1.3次 vs . 0.7次住院,p = 0.035),但总体急性加重率相同(4.6次 vs . 4.3次,p = 0.58)。铜绿假单胞菌定植的独立预测因素是预测的FEV1百分比低(比值比2.46;95%置信区间1.27 - 4.77)和多种微生物定植(比值比:4.07;95%置信区间1.56 - 10.58)。17例(11%)患者感染了多重耐药菌株;然而,无一例为泛耐药。
与流感嗜血杆菌相比,铜绿假单胞菌的持续感染率更高,住院次数更多。然而,急性加重率相似;因此,流感嗜血杆菌导致显著的门诊发病率。铜绿假单胞菌感染发生在肺功能损害的所有分层中,但在支气管扩张中很少多重耐药。即使对于肺功能保存良好的患者,也需要仔细的微生物学随访。